Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Idiopathic Pulmonary Fibrosis. Core disease mechanisms, molecular and cell...

This report is retrieval-only and is generated directly from Asta results.

• Papers retrieved: 18
• Snippets retrieved: 20

Relevant Papers

[1] Comorbidity of Pulmonary Fibrosis and COPD/Emphysema: Research Status, Trends, and Future Directions --------- A Bibliometric Analysis from 2004 to 2023

• Authors: H. Fang, Tairan Dong, Zhuojun Han, Shanlin Li, Mingfei Liu et al.
• Year: 2023
• Venue: International Journal of Chronic Obstructive Pulmonary Disease
• URL: https://www.semanticscholar.org/paper/e9e39dadd7fb76d988cbc101b957517276f55d7f
• DOI: 10.2147/COPD.S426763
• PMID: 37720874
• PMCID: 10505036
• Citations: 4
• Summary: The research hotspots and trends identified in this study provide a reference for in-depth research in this field, aiming to promote the development of the comorbidity of pulmonary fibrosis and COPD/emphysema.
• Evidence snippets:
• Snippet 1 (score: 0.701) > Cluster #0 explores clinical conditions associated with pulmonary fibrosis, including idiopathic interstitial pneumonia, idiopathic fibrosis, and pulmonary fibrosis combined with emphysema. This cluster establishes more precise classification and diagnostic criteria for these conditions, distinguishing them from one another, and emphasizes the necessity of actively pursuing accurate diagnosis and treatment strategies in clinical research. 1][22][23] Cluster #1 primarily focuses on the latest clinical research concerning idiopathic pulmonary fibrosis, encompassing clinical classification, diagnostic criteria, cutting-edge methodologies, the influence of comorbidities on disease progression, and the effectiveness of various drug treatment modalities. ][26][27] The following clusters are dedicated to studying the pathogenesis of related diseases, including idiopathic fibrosis, by investigating genes, signaling pathways, cellular mechanisms, and more. Cluster #2 focuses on elucidating the mechanisms of cellular senescence in idiopathic fibrosis. Lung senescence, characterized by an increased number of senescent cells, is believed to directly contribute to various age-related respiratory diseases. Targeting cellular senescence through therapeutic interventions could potentially delay or even reverse age-related respiratory diseases. 9][30] Cluster #3 primarily engages in fundamental research on the cellular and molecular mechanisms underlying pulmonary fibrosis. It investigates related genes, regulatory factors, and cellular pathways to gain a deeper understanding of the pathogenic mechanisms of this disease. ][33][34] Cluster #7 delves into the intricate cellular and molecular mechanisms underlying pulmonary fibrosis. It focuses on tissue remodeling, structural alterations in fibrotic lesions, and aberrant cell populations. 6][37][38] Cluster #8 explores the cellular and molecular mechanisms of lung tissue and their implications for treatments. It demonstrates that age-related lung diseases share common mechanisms, such as telomere shortening, abnormal tissue remodeling, and functional damage. 0][41] Cluster #9 investigates the crucial role of Redox regulatory proteins, oxidative stress, and inflammatory response in the pathogenesis of pulmonary diseases, including pulmonary fibrosis.

[2] The evolution of in vitro models of lung fibrosis: promising prospects for drug discovery

• Authors: Emanuel Kolanko, Anna Cargnoni, Andrea Papait, A. Silini, P. Czekaj et al.
• Year: 2024
• Venue: European Respiratory Review
• URL: https://www.semanticscholar.org/paper/b4406eb865ebf9edad815c6b363dbb5ace4f8679
• DOI: 10.1183/16000617.0127-2023
• PMID: 38232990
• PMCID: 10792439
• Citations: 32
• Summary: In vitro lung fibrosis models have progressively improved to represent tools closely mimicking pathological processes and allow advancements of personalised medicine and enhance comprehension of pathogenic molecular mechanisms.
• Evidence snippets:
• Snippet 1 (score: 0.550) > Lung fibrosis is a complex process, with unknown underlying mechanisms, involving various triggers, diseases and stimuli. Different cell types (epithelial cells, endothelial cells, fibroblasts and macrophages) interact dynamically through multiple signalling pathways, including biochemical/molecular and mechanical signals, such as stiffness, affecting cell function and differentiation. Idiopathic pulmonary fibrosis (IPF) is the most common fibrosing interstitial lung disease (fILD), characterised by a notably high mortality. Unfortunately, effective treatments for advanced fILD, and especially IPF and non-IPF progressive fibrosing phenotype ILD, are still lacking. The development of pharmacological therapies faces challenges due to limited knowledge of fibrosis pathogenesis and the absence of pre-clinical models accurately representing the complex features of the disease. To address these challenges, new model systems have been developed to enhance the translatability of preclinical drug testing and bridge the gap to human clinical trials. The use of two- and three-dimensional in vitro cultures derived from healthy or diseased individuals allows for a better understanding of the underlying mechanisms responsible for lung fibrosis. Additionally, microfluidics systems, which replicate the respiratory system's physiology ex vivo, offer promising opportunities for the development of effective therapies, especially for IPF. Tweetable abstract In vitro lung fibrosis models have progressively improved to represent tools closely mimicking pathological processes and allow advancements of personalised medicine and enhance comprehension of pathogenic molecular mechanisms. https://bit.ly/40P8gqw
• Snippet 2 (score: 0.510) > Additionally, there are transgenic models in which specific gene mutations associated with ILD, such as a mutant surfactant protein C gene (SFTPC) in alveolar type II (AT2) cells [16], are triggered to induce the development of pulmonary fibrosis. In addition, the bleomycin-induced pulmonary fibrosis model is widely used and well characterised [17]. This model has proven valuable in the exploration of novel pathogenic mechanisms that may have relevance to human disease. Notably, recent research has demonstrated the pivotal role of RNA-binding motif protein 7 (RBM7) in fibrosis onset [18]. Nevertheless, these models present notable limitations [19], possibly for the fact that all animal models of IPF are artificially induced using single agents or target a single cell type, while it is well known that the pathogenesis is multifactorial and still remains elusive. > In this context, in vitro models, despite being a simplified representation of actual diseased tissue, can be valuable because they allow for the identification of specific cellular and molecular mechanisms that trigger and induce disease progression. > Nonetheless, as they continue to evolve, in vitro models are increasingly approaching the complexity of in vivo systems. For example, lung organoids derived from induced pluripotent stem cells (iPSCs) obtained from patients enable monitoring of the alterations acquired by the different cell populations during the disease progression. This approach aids in pinpointing the specific states of maturation where issues may arise. Moreover, the use of human material, with a personalised medicine perspective, enables the screening of drugs, including off-label drugs, for drug repurposing. In recent years, in vitro models have been developed to improve preclinical drug testing and bridge the translational gap to human clinical trials. These techniques offer advanced imaging and analysis of disease mechanisms, allowing for drug discovery and validation in a personalised manner (figure 2 and table 1). This is a comprehensive overview of the various in vitro models that are accessible for studying the molecular mechanisms underlying fibrosis pathogenesis, as well as their applications in drug screening.

[3] Cellular Senescence in Lung Fibrosis

• Authors: Fernanda Hernández-González, R. Faner, M. Rojas, A. Agustí, M. Serrano et al.
• Year: 2021
• Venue: International Journal of Molecular Sciences
• URL: https://www.semanticscholar.org/paper/072814da23bd69a06a991e6dce8d86d029925578
• DOI: 10.3390/ijms22137012
• PMID: 34209809
• PMCID: 8267738
• Citations: 61
• Influential citations: 1
• Summary: Current and emerging therapeutic approaches to treat fibrosing ILDs by targeting cellular senescence are highlighted, and the idea that it also drives degenerative processes such as lung fibrosis is strengthened.
• Evidence snippets:
• Snippet 1 (score: 0.549) > For several decades, understanding lung fibrosis as a process that limits lifespan has challenged scientists. Progressive loss of lung function due to pulmonary fibrosis contributes significantly to the ever-increasing burden of chronic disease throughout the world. Around half of deaths in the developed world are attributable to fibrotic diseases, including idiopathic pulmonary fibrosis (IPF), the most common fibrotic interstitial lung disease (ILD) characterized by progressive and irreversible respiratory failure and death [1,2]. The phenomenological complexity existing in the lung fibrosis process has led, over the years, to a rising number of hypotheses about the specific cellular and molecular causes. The most prominent feature of lung fibrosis is a gradual age-related loss of function that occurs at the molecular, cellular, and tissue levels. The lack of somatic maintenance and repair functions and the stochastic enforcement of damage may explain the marked variability of cellular mechanisms that appear to be involved in aging phenotypes, such as lung fibrosis [3,4]. > Fibrosis and wound healing are essentially interwoven processes, driven by a cascade of injury, inflammation, fibroblast proliferation and migration, matrix deposition and remodelling. Pathological fibrogenesis that occurs in many diverse organs and diseases is a dynamic process involving complex interactions between epithelial cells, fibroblasts, immune cells (macrophages, T-cells), and/or endothelial injuries [5,6]. There are many extrinsic hazards known to induce injury to lung epithelium-infections, exposures to organic or inorganic components, cigarette smoking, and so forth-while there is also damage of unknown aetiology. As a response to lung injury, many interrelated woundhealing pathways are activated in order to facilitate the repair, turnover, and adaptation of lung tissue [7]. However, although their aetiology and causative mechanisms varies, the different fibrotic lung diseases all fail to properly eliminate inciting factors, leading to continued tissue damaging with an abnormal and exaggerated accumulation of extracellular matrix (ECM) components and collagen deposition.

[4] Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

• Authors: T. Phan, P. Paliogiannis, Gheyath K Nasrallah, Roberta Giordo, A. Eid et al.
• Year: 2020
• Venue: Cellular and Molecular Life Sciences: CMLS
• URL: https://www.semanticscholar.org/paper/60ab2fce378cefe715daabd6fdd84f8a31c65c7a
• DOI: 10.1007/s00018-020-03693-7
• PMID: 33201251
• PMCID: 7669490
• Citations: 269
• Influential citations: 9
• Summary: An update is provided regarding the emerging cellular and molecular mechanisms involved in the onset and progression of idiopathic pulmonary fibrosis.
• Evidence snippets:
• Snippet 1 (score: 0.548) > Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, is a progressive, irreversible, and typically lethal disease characterized by an abnormal fibrotic response involving vast areas of the lungs. Given the poor knowledge of the mechanisms underpinning IPF onset and progression, a better understanding of the cellular processes and molecular pathways involved is essential for the development of effective therapies, currently lacking. Besides a number of established IPF-associated risk factors, such as cigarette smoking, environmental factors, comorbidities, and viral infections, several other processes have been linked with this devastating disease. Apoptosis, senescence, epithelial-mesenchymal transition, endothelial-mesenchymal transition, and epithelial cell migration have been shown to play a key role in IPF-associated tissue remodeling. Moreover, molecules, such as chemokines, cytokines, growth factors, adenosine, glycosaminoglycans, non-coding RNAs, and cellular processes including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, hypoxia, and alternative polyadenylation have been linked with IPF development. Importantly, strategies targeting these processes have been investigated to modulate abnormal cellular phenotypes and maintain tissue homeostasis in the lung. This review provides an update regarding the emerging cellular and molecular mechanisms involved in the onset and progression of IPF.
• Snippet 2 (score: 0.530) > Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, is an irreversibly progressive and usually lethal disease. IPF patients typically succumb to respiratory failure secondary to loss of respiratory function from extensive fibrotic scarring of the lung parenchyma. Following diagnosis, the average life expectancy is 3-5 years. IPF is more common in males and individuals older than 60 years. The histopathological hallmarks include subpleural fibrosis, subepithelial fibroblastic foci, and microscopic honeycombing [1][2][3][4]. The clinical progress is usually complicated by acute episodes of respiratory function deterioration, termed IPF exacerbations. No effective treatments are available in preventing and controlling the acute exacerbations of IPF [5,6]. The most common complications of IPF include lung cancer, depression, pulmonary hypertension, muscle weakness, heart failure, thrombosis, acute respiratory distress syndrome (ARDS), and respiratory failure. The recent introduction of two anti-fibrotic drugs, pirfenidone and nintedanib, will likely lead to a significant retardation in lung-function decline and a reduction in the incidence and severity of associated complications. However, as these agents are not curative, new therapeutic approaches are needed [7] Given that the exact pathophysiological mechanisms involved in IPF remain elusive. Additional studies on the cellular processes and molecular pathways involved are essential for the development of effective IPF therapies. A number of processes and factors, such as the role of aging and cellular apoptosis, oxidative stress, endoplasmic reticulum stress, cellular plasticity, and noncoding RNAs are the focus of intense research. Their better understanding might lead to the effective modulation of aberrant cellular processes and the maintenance of tissue homeostasis in the lung. This review discusses the key evolving concepts in IPF pathogenesis, the cellular and molecular mechanisms involved in the onset and progression of the disease, and the identification and development of novel targeted therapies.

[5] Targeting Chitinase 1 and Chitinase 3-Like 1 as Novel Therapeutic Strategy of Pulmonary Fibrosis

• Authors: S. Lee, Chang-min Lee, B. Ma, Suchitra Kamle, J. Elias et al.
• Year: 2022
• Venue: Frontiers in Pharmacology
• URL: https://www.semanticscholar.org/paper/8cc7e64fb666492633849749ee3952faf632dac9
• DOI: 10.3389/fphar.2022.826471
• PMID: 35370755
• PMCID: 8969576
• Citations: 20
• Summary: Specific roles and regulatory mechanisms of CHIT1 and CHI3L1 in profibrotic cell and tissue responses as novel therapeutic targets of pulmonary fibrosis are discussed.
• Evidence snippets:
• Snippet 1 (score: 0.541) > Tissue fibrosis is a major cause of morbidity in pulmonary fibrosis. As a normal repair response, fibrosis is a series of process of cellular damage caused by various conditions that initiate inflammation, recruitments of inflammatory cells, followed by final tissue repair and termination of inflammation. Loss of regulatory signals and imbalance in the process of wound healing leads to aberrant activation of repair response, causing pathologic fibrosis in various organs including lung, resulting in a disease state (Wilson and Wynn, 2009). Since excellent review articles detailing the molecules and signaling pathways involved in the pathogenesis of pulmonary fibrosis are already available (Micallef et al., 2012;Wolters et al., 2014;Sgalla et al., 2018;Strykowski and Adegunsoye, 2021), in this section, we only focus on the discussion of major factors leading to pathologic fibrosis, that can be also regulated by CHIT1 or CHI3L1 in the development and progression of pulmonary fibrosis. Pulmonary fibrosis comprises a number of different etiologies and pathologies with completely different clinical features and therapeutic responses. Accordingly, there are significant limitations in identifying common pathogenetic mechanisms of pulmonary fibrosis. This is particularly true for in vitro cell or in vivo preclinical animal models of pulmonary fibrosis, since currently no preclinical models are exactly representing the characteristic cellular and tissue responses of IPF and other interstitial lung disease (ILD). In addition, so far relatively small number of human studies with dysregulated expression of CHIT1 and/or CHI3L1 in the patients with IPF and ILD add certain limitations in direct clinical translation of preclinical data. With these limitations in mind, here the molecular and mechanistic implications of CHIT1 and CHI3L1 as potential therapeutic targets are discussed based on up-to-dated and common lung pathologies of pulmonary fibrosis.

[6] Cellular and Molecular Genetic Mechanisms of Lung Fibrosis Development and the Role of Vitamin D: A Review

• Authors: Darya Enzel, M. Kriventsov, T. Sataieva, V. Malygina
• Year: 2024
• Venue: International Journal of Molecular Sciences
• URL: https://www.semanticscholar.org/paper/fc44de05d17a984b1918bf7d7db585d16b6dc7dd
• DOI: 10.3390/ijms25168946
• PMID: 39201632
• PMCID: 11355055
• Citations: 6
• Summary: This literature review presents the key modern concepts concerning molecular genetics and cellular mechanisms of lung fibrosis development, based mainly on in vitro and in vivo studies in experimental models of bleomycin-induced pulmonary fibrosis, as well as the latest data on metabolic features, potential targets, and effects of vitamin D and its metabolites.
• Evidence snippets:
• Snippet 1 (score: 0.526) > Idiopathic pulmonary fibrosis remains a relevant problem of the healthcare system with an unfavorable prognosis for patients due to progressive fibrous remodeling of the pulmonary parenchyma. Starting with the damage of the epithelial lining of alveoli, pulmonary fibrosis is implemented through a cascade of complex mechanisms, the crucial of which is the TGF-β/SMAD-mediated pathway, involving various cell populations. Considering that a number of the available drugs (pirfenidone and nintedanib) have only limited effectiveness in slowing the progression of fibrosis, the search and justification of new approaches aimed at regulating the immune response, cellular aging processes, programmed cell death, and transdifferentiation of cell populations remains relevant. This literature review presents the key modern concepts concerning molecular genetics and cellular mechanisms of lung fibrosis development, based mainly on in vitro and in vivo studies in experimental models of bleomycin-induced pulmonary fibrosis, as well as the latest data on metabolic features, potential targets, and effects of vitamin D and its metabolites.

[7] Translational control of the fibroblast-extracellular matrix association

• Authors: R. Nho, V. Polunovsky
• Year: 2013
• Venue: Translation
• URL: https://www.semanticscholar.org/paper/9761d71436d581f1a9fae8de80d2a797b79bf162
• DOI: 10.4161/trla.23934
• PMID: 26824013
• PMCID: 4718055
• Citations: 10
• Summary: Evidence is presented indicating that the dysregulation of the eIF4F-mediated translational apparatus is an important factor in the development and progression of IPF and other fibrotic disorders.
• Evidence snippets:
• Snippet 1 (score: 0.524) > Pulmonary fibrosis can be a complication of a group of lung disorders called interstitial lung diseases (ILDs). 1 In cases when pulmonary fibrosis develops within the lung in the absence of any known provocations, it is termed idiopathic pulmonary fibrosis (IPF), which is also known as cryptogenic fibrosing alveolitis (CFA). IPF is characterized by abnormal expansion of granulation tissue due to excessive production of ECM, hyperpropagation of stromal fibroblasts and vast scarring of normal lung parenchyma leading to a deficiency in gas exchange. IPF is usually fatal with life expectance within 2 to 6 y following diagnosis. 2 Although there has been some progress in understanding the pathogenesis of IPF, there is still no proven effective therapy Pulmonary fibrosis is a severe lung disease characterized by sustained propagation of lung fibroblasts and relentless accumulation of extracellular matrix (ECM). Idiopathic pulmonary fibrosis (IPF) is the most severe chronic form of pulmonary fibrosis and results both in the gradual exchange of normal lung parenchyma with fibrotic tissue and in the irreversible impairment of gas exchange in the lung. Despite the urgency for novel therapies in IPF treatment, there is no effective and proven medical therapy available. Molecular mechanisms underlying IPF pathogenesis include aberrant ECM signaling through the canonical integrin/PI3K/Akt/ mTORC1 signal transduction pathway. One important and well-characterized downstream effector of this pathway is the cellular protein synthesis machinery. Here we will review the recent advances in our understanding of the function of ECM and integrin receptor signaling in development of IPF and will present evidence indicating that the dysregulation of the eIF4F-mediated translational apparatus is an important factor in the development and progression of IPF and other fibrotic disorders. We further discuss the perspectives and challenges to curbing this deadly disease by targeting aberrant translation. > available and lung transplantation is the only viable intervention in end-stage disease.

[8] Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways

• Authors: V. Suryadevara, R. Ramchandran, D. Kamp, V. Natarajan
• Year: 2020
• Venue: International Journal of Molecular Sciences
• URL: https://www.semanticscholar.org/paper/9ad48e612a124c8c4940043f4bae96946d26afc7
• DOI: 10.3390/ijms21124257
• PMID: 32549377
• PMCID: 7352853
• Citations: 108
• Influential citations: 5
• Summary: The current understanding of the role and signaling pathways of prostanoids, lysophospholipids, and sphingolipid metabolism and their metabolizing enzymes in the development of lung fibrosis is described.
• Evidence snippets:
• Snippet 1 (score: 0.523) > Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown etiology characterized by distorted distal lung architecture, inflammation, and fibrosis. The molecular mechanisms involved in the pathophysiology of IPF are incompletely defined. Several lung cell types including alveolar epithelial cells, fibroblasts, monocyte-derived macrophages, and endothelial cells have been implicated in the development and progression of fibrosis. Regardless of the cell types involved, changes in gene expression, disrupted glycolysis, and mitochondrial oxidation, dysregulated protein folding, and altered phospholipid and sphingolipid metabolism result in activation of myofibroblast, deposition of extracellular matrix proteins, remodeling of lung architecture and fibrosis. Lipid mediators derived from phospholipids, sphingolipids, and polyunsaturated fatty acids play an important role in the pathogenesis of pulmonary fibrosis and have been described to exhibit pro- and anti-fibrotic effects in IPF and in preclinical animal models of lung fibrosis. This review describes the current understanding of the role and signaling pathways of prostanoids, lysophospholipids, and sphingolipids and their metabolizing enzymes in the development of lung fibrosis. Further, several of the lipid mediators and enzymes involved in their metabolism are therapeutic targets for drug development to treat IPF.

[9] Molecular pathways in idiopathic pulmonary fibrosis pathogenesis: Transcending barriers to optimally targeted pharmacotherapies

• Authors: R. Strykowski, A. Adegunsoye
• Year: 2021
• Venue: EBioMedicine
• URL: https://www.semanticscholar.org/paper/3f70120771654984a132710d119c3cee6849ff0b
• DOI: 10.1016/j.ebiom.2021.103373
• PMID: 33965873
• PMCID: 8114113
• Citations: 1
• Summary: An array of mechanisms involved in the pathophysiologic progression of previously normal lung tissue to fibrosis in IPF are examined, linking the molecular and cellular events associated with this complex disease.
• Evidence snippets:
• Snippet 1 (score: 0.519) > Although the survival of patients with idiopathic pulmonary fibrosis (IPF) still hovers around a median of two to five years, [1] the therapeutic landscape of this devastating interstitial lung disease is encumbered by a paucity of effective pharmacotherapies. Widely used anti-fibrotic medications slow the rate of functional decline [2,3] but are often associated with adverse effects and persistently high symptom burden. As the pathophysiologic mechanisms underlying fibrosis are yet to be fully elucidated, our understanding of disease progression in IPF remains stifled, posing substantial limitations to the potential value that could be gained from more novel therapies targeting these mechanisms. Prior genome-wide associated studies evaluating the genetic profiles of affected patients have identified several notable variants and risk polymorphisms associated with IPF pathogenesis. [4] Likewise, recent epigenomic, transcriptomic, and proteomic data have helped to generate a single-cell atlas of IPF defining key molecular factors and pathways in the progression of fibrosis. [5] Other histopathologic analyses and investigations focused on immunophenotyping have identified phenotypically distinct CD4 + T cell infiltrates within the lung tissue in patients with IPF. [6] From a macroscopic perspective, recent investigations have found a significant loss of terminal bronchioles in lung tissue obtained from patients with IPF, implicating the small airways in this disease. [7] Taken together, these underscore numerous efforts that further illuminate the pathophysiology of this complex disease, with the overall goal of identifying optimal therapeutic targets and improving currently existing ones. > In this issue of EBioMedicine, Xu and colleagues [8] examine an array of mechanisms involved in the pathophysiologic progression of previously normal lung tissue to fibrosis in IPF. [8] Their novel and exciting findings link the molecular and cellular events associated with IPF to the concomitant structural and histological events.

[10] Bleomycin-Induced Fibrosis and the Effectiveness of Centella Asiatica as a Treatment

• Authors: N. Soeroso, M. Ichwan, A. S. Wahyuni, C. Mariedina, Yabestin Pakpahan
• Year: 2024
• Venue: Journal of Experimental Pharmacology
• URL: https://www.semanticscholar.org/paper/d54d6d4e0d4a082eaac34ebd0bc406fdd20850ca
• DOI: 10.2147/JEP.S463899
• PMID: 39345799
• PMCID: 11438459
• Citations: 3
• Summary: The induction of bleomycin 4 mg/kg/BB was proven to cause fibrosis in the lungs of rats, and Centella asiatica extract was used as a treatment and further research regarding antifibrotic drugs is hoped to reduce fibrotic areas significantly.
• Evidence snippets:
• Snippet 1 (score: 0.517) > Fibrosis is the most common interstitial lung disease defined by regular interstitial pneumonia histological pattern. 1 Idiopathic pulmonary fibrosis is a lung disorder where scar tissue is found in the lungs, however, the cause is still unknown. Pulmonary fibrosis patients may have a poor prognosis compared to other malignancies. Untreated pulmonary fibrosis can progress to CPD (Chronic Lung Disease), resulting in tissue death. 2 Data on the incidence of pulmonary fibrosis varies, in the United States, it is 6.8-8.8 per 100,000 population per year, Europe 0.22-7.4 per 10,000 population, and the incidence of fibrosis increases with age. 3,4 leomycin is a compound produced by Streptomyces verticillus bacteria, and the bacteria is often used in trial animal interventions. Bleomycin is often used in chemotherapy, but this compound has the side effect of being toxic to lung cells. The mechanism of bleomycin toxicity has been tested in vitro. Side effects of using bleomycin include nausea, fever, vomiting, and allergies. Treatment with bleomycin can also cause interstitial pneumonitis and pulmonary fibrosis. 5 nimal models are crucial to the study of disease, and lung pathobiology is studied using many different models. Over time, numerous models of pulmonary fibrosis have been created. Common techniques include silica or asbestos, radiation damage, bleomycin, transgenic mice, and gene transfer via fibrogenic cytokines. As of right now, bleomycin is the mechanism employed to cause experimental lung fibrosis in animals. 6 egrettably, lung damage resulting from pulmonary fibrosis is irreversible and permanent. The lungs may function better if the condition is identified early and treated. The majority of pulmonary fibrosis therapies aim to enhance quality of life and reduce symptoms. Lung illness fibroproliferative is common and has a high death rate. Inflammation, mesenchymal cell proliferation, and the deposition of interstitial matrix constituents including collagen and fibronectin are all involved in the pathophysiology of fibrotic lung disease.

[11] Lung regeneration: diverse cell types and the therapeutic potential

• Authors: Yutian Chen, Zhen Li, Gaili Ji, Shaochi Wang, Chunheng Mo et al.
• Year: 2024
• Venue: MedComm
• URL: https://www.semanticscholar.org/paper/0fbe00de4b129b66ffcc63fd4298d45dc0352a8c
• DOI: 10.1002/mco2.494
• PMID: 38405059
• PMCID: 10885188
• Citations: 27
• Summary: A review of the molecular and cellular mechanisms of lung regeneration, drug development, and clinical trials provides a reference for further research on the molecular and cellular mechanisms of lung regeneration, drug development, and clinical trials.
• Evidence snippets:
• Snippet 1 (score: 0.512) > Abstract Lung tissue has a certain regenerative ability and triggers repair procedures after injury. Under controllable conditions, lung tissue can restore normal structure and function. Disruptions in this process can lead to respiratory system failure and even death, causing substantial medical burden. The main types of respiratory diseases are chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and acute respiratory distress syndrome (ARDS). Multiple cells, such as lung epithelial cells, endothelial cells, fibroblasts, and immune cells, are involved in regulating the repair process after lung injury. Although the mechanism that regulates the process of lung repair has not been fully elucidated, clinical trials targeting different cells and signaling pathways have achieved some therapeutic effects in different respiratory diseases. In this review, we provide an overview of the cell type involved in the process of lung regeneration and repair, research models, and summarize molecular mechanisms involved in the regulation of lung regeneration and fibrosis. Moreover, we discuss the current clinical trials of stem cell therapy and pharmacological strategies for COPD, IPF, and ARDS treatment. This review provides a reference for further research on the molecular and cellular mechanisms of lung regeneration, drug development, and clinical trials.

[12] The Mechanism of Oxidative Stress in Pulmonary Fibrosis and Research Progress

• Authors: Duo Xu, Qian Wang, Meng Lyu, Chunyu Huang, Xianglin Yuan et al.
• Year: 2026
• Venue: Antioxidants
• URL: https://www.semanticscholar.org/paper/54c6c9cba7e158d270ee82da0a58117282c8ae40
• DOI: 10.3390/antiox15010142
• PMID: 41596200
• PMCID: 12837592
• Citations: 1
• Summary: This review summarizes the regulatory mechanisms of oxidative stress in pulmonary fibrosis, with a focus on its critical role in inducing and promoting fibrosis through relevant target cells and signaling pathways.
• Evidence snippets:
• Snippet 1 (score: 0.511) > Pulmonary fibrosis (PF) is a group of chronic progressive lung diseases characterized by irreversible remodeling of lung tissue structure, abnormal proliferation of fibroblasts, and excessive deposition of extracellular matrix (ECM), among which idiopathic pulmonary fibrosis (IPF) is the most typical subtype. Currently, the only two clinically approved therapeutic drugs (nintedanib and pirfenidone) can only partially slow disease progression without reversing fibrotic lesions, and are associated with varying degrees of adverse effects. Oxidative stress, defined as a pathological imbalance between systemic oxidant and antioxidant systems, has been substantiated by extensive research as a pivotal mechanism driving the pathogenesis and progression of pulmonary fibrosis. This review summarizes the regulatory mechanisms of oxidative stress in pulmonary fibrosis, with a focus on its critical role in inducing and promoting fibrosis through relevant target cells and signaling pathways. We also specifically highlight the latest progress and challenges in therapeutic strategies targeting oxidative stress, and discuss next-generation therapies, including the modulation of endogenous antioxidant pathways, supplementation of exogenous antioxidants, as well as nanomaterials, exosomes, and combination therapies. We hope this review will deepen the understanding of oxidative stress and pulmonary fibrosis, and provide new directions for improving the clinical efficacy of oxidative stress-targeted therapies.

[13] Evaluation of Proteasome Inhibitors in the Treatment of Idiopathic Pulmonary Fibrosis

• Authors: I. Chen, Yi-Ching Liu, Yen-Hsien Wu, S. Lo, Z. Dai et al.
• Year: 2022
• Venue: Cells
• URL: https://www.semanticscholar.org/paper/1254ef188f65fe4aacc0fbc21eb4ea91c5256fba
• DOI: 10.3390/cells11091543
• PMID: 35563849
• PMCID: 9099509
• Citations: 12
• Summary: This review summarizes the current research on proteasome inhibitors for pulmonary fibrosis, and provides a reference for whether proteasomal inhibition have the potential to become new drugs for the treatment of lung fibrosis.
• Evidence snippets:
• Snippet 1 (score: 0.510) > Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and usually lethal disease characterized by an abnormal fibrotic response involving large areas of the lungs. Risk factors associated with IPF include smoking, environmental factors, comorbidities, and viral infections [1]. Most patients have persistent dyspnea and limited exercise tolerance resulting in a poor quality of life. Many patients develop pulmonary hypertension and are at an increased risk of pulmonary embolism and sudden cardiac death [2]. The molecular mechanisms underlying the pathogenesis and development of IPF are unclear, however molecules including chemokines, cytokines, growth factors, adenosine, glycosaminoglycans, and non-coding RNA, and cellular processes, including apoptosis, senescence, hypoxia, endothelial-mesenchymal transition, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and alternative polyadenylation have been linked with the development of IPF [3]. Pirfenidone and nintedanib are the mainstays of current medical treatment of IPF, however they do not completely prevent or improve lung function. It is essential to find additional drugs that can effectively reduce the pro-fibrotic maturation of lung fibroblasts, and ultimately prevent IPF progression. Understanding the molecular mechanisms of IPF will aid in drug discovery. The wound healing response induced by Intrinsic risk factors including genetic susceptibility, aging, male sex, the lung microbiome, and comorbidities have been associated with the pathogenesis of IPF [8]. The susceptibility genes associated with the pathogenesis of IPF are currently classified into four categories: (1) genes related to alveolar stability (such as SFTPC, SFTPA1, SFTPA2);

[14] Are mast cells instrumental for fibrotic diseases?

• Authors: C. Overed-Sayer, L. Rapley, T. Mustelin, D. Clarke
• Year: 2014
• Venue: Frontiers in Pharmacology
• URL: https://www.semanticscholar.org/paper/706efd587a7fd74ae41d832bf0427b99755c3ea9
• DOI: 10.3389/fphar.2013.00174
• PMID: 24478701
• PMCID: 3896884
• Citations: 98
• Influential citations: 6
• Summary: The mast cell is discussed and its physiological role in tissue repair and remodeling, as well as its pathological role in fibrotic diseases such as IPF, where the process of tissue repairand remodeling is thought to be dysregulated.
• Evidence snippets:
• Snippet 1 (score: 0.505) > Idiopathic pulmonary fibrosis is a devastating disease for the patient. There is currently no effective treatment for this disease and the prognosis is bleak. As the term "idiopathic" indicates, the causes of the disease are unknown, as are the molecular mechanisms underpinning initiation and progression of the condition. Clearly, fibrotic processes play a key role in driving the relentless destruction of alveolar integrity, resulting eventually in a declining ability of the lung to oxygenate the blood. This decline is the root cause of the deteriorating health of the patient once the disease passes from its typically undiagnosed, early phase, into its clinically symptomatic phase. Within less than 3 years in most patients have lost much of their respiratory capacity and require drastic measures to survive. > The pharmaceutical and biotechnology industry has made many attempts to find effective treatments for IPF, but the disease has so far defied all attempts at therapeutic intervention. Clinical trial failures may arise for many reasons, including disease heterogeneity, lack of readily measurable clinical end points other than overall survival, and, perhaps most of all, a lack of understanding of the underlying molecular mechanisms of the progression of IPF. > On the positive side, with emerging new insights into the pathways and cell types involved in IPF come new opportunities for therapeutic intervention. Technologies for molecular profiling of patient tissue samples are already revealing many hitherto unexpected aspects of the disease pathology. Several new cell types, including the myofibroblast and the mast cell, offer therapeutic possibilities not previously exploited. However, the only conclusive way to determine if these cells are important for the pathogenesis of IPF is to target them with sufficiently powerful therapeutics and determine the impact on disease progression in phase 2 clinical trials. Another potentially helpful way to success may be that new therapeutics are first tested in other fibrotic conditions than IPF. Based on our current understanding of disease mechanisms, it appears likely that therapeutic interventions that are efficacious in one form of fibrotic disease will be efficacious in other fibrotic conditions. Thus, the clinically most feasible disease indication may serve as a first read-out to support the testing in more challenging indications, such as IPF. This may well be the case for mast cell-targeted therapies.

[15] The Role of Mitochondrial DNA in Mediating Alveolar Epithelial Cell Apoptosis and Pulmonary Fibrosis

• Authors: S. Kim, P. Cheresh, R. Jablonski, David B. Williams, D. Kamp
• Year: 2015
• Venue: International Journal of Molecular Sciences
• URL: https://www.semanticscholar.org/paper/2928a04f743ee87fdaa9439048757c7aa1d89ea3
• DOI: 10.3390/ijms160921486
• PMID: 26370974
• PMCID: 4613264
• Citations: 111
• Influential citations: 3
• Summary: A conceptual model of how SIRTs modulate reactive oxygen species (ROS)-driven mitochondrial metabolism that may be important for their tumor suppressor function is presented and suggests novel therapeutic targets that may prove useful for the management of age-related diseases, including pulmonary fibrosis and lung cancer.
• Evidence snippets:
• Snippet 1 (score: 0.502) > Pulmonary fibrosis is characterized by an over abundant accumulation of extracellular matrix (ECM) collagen deposition in the distal lung interstitial tissue in association with an injured overlying epithelium and activated myofibroblasts. Idiopathic pulmonary fibrosis (IPF) is the most common variety of lung fibrosis and carries a sobering mortality approaching 50% at 3-4 years [1]. Although many of the cellular and molecular mechanisms underlying the pathophysiology of lung fibrosis have emerged from numerous studies over the past several decades, the precise pathways involved, their regulation, and the role of crosstalk between cells are not fully understood. With the exception of two FDA-approved drug therapies (pirfenidone and nintenanib) emerging in the fall of 2014, there are no effective therapies for patients with IPF. Furthermore, these two drugs primarily slow disease progression rather than improve lung function or symptoms. A better understanding of the pathobiology of pulmonary fibrosis is critically important in the design of more useful therapies. > As will be reviewed herein, the extent of alveolar epithelial cell (AEC) injury, repair, and aging are emerging as critical determinants underlying pulmonary fibrosis. The purpose of this review is to highlight our current understanding of the causal role of AEC mitochondrial DNA (mtDNA) damage following oxidative stress in promoting AEC apoptosis and pulmonary fibrosis. Although oxidative mtDNA damage in other cell types (i.e., vascular endothelial cells, macrophages, fibroblasts, etc.) are likely important, we concentrate on the lung epithelium given its prominent role in the pathophysiology of lung fibrosis. In particular, we focus on asbestosis (pulmonary fibrosis arising following asbestos exposure) as it shares radiographic and pathologic features with IPF though IPF is more common and carries a worse prognosis. Our group is using the asbestos paradigm to better understand the pathophysiologic mechanisms underlying pulmonary fibrosis.

[16] Genome-Wide Transcriptional Response During the Development of Bleomycin-Induced Pulmonary Fibrosis in Sprague-Dawley Rats

• Authors: Han-Jin Park, Mi-Jin Yang, Jung-Hwa Oh, Young-Su Yang, M. Kwon et al.
• Year: 2010
• Venue: Toxicological Research
• URL: https://www.semanticscholar.org/paper/6c1484630c31abb392dd75998dcdefd244abf882
• DOI: 10.5487/TR.2010.26.2.137
• PMID: 24278517
• PMCID: 3834473
• Citations: 5
• Influential citations: 1
• Summary: Global gene expression analysis revealed significantly altered expression of genes in a time-dependent manner during the development of pulmonary fibrosis, and the expression of triggering receptor expressed on myeloid cells 2, secreted phosphoprotein 1, and several proteases was considerably induced in the lung after bleomycin treatment.
• Evidence snippets:
• Snippet 1 (score: 0.501) > Idiopathic pulmonary fibrosis is a consequence of abnormal tissue repair, which is characterized by extensive inflammation in the interstitial and alveolar spaces, proliferation of fibroblasts, and progressive fibrosis leading to the destruction of lung function (Selman et al., 2004). Pulmonary fibrosis involves cytokine networks and cellular interactions among several cell types, which results in increased collagen gene expression and collagen deposition in the lungs (Piguet et al., 1990;. Despite many investigations on the pathogenesis of pulmonary fibrosis and its relationship to immune cells, extracellular matrix repair, cytokines, and chemokines, the molecular mechanisms underlying this disease remain unclear (Zhang et al., 1994(Zhang et al., , 1996Kuwano et al., 2001;Gharaee-kermani et al., 2008). > Bleomycin is a useful chemotherapeutic antitumor drug, derived from Streptomyces verticillus; however, as a side effect, bleomycin treatment may lead to pulmonary fibrosis in humans and animals. Therefore, animal models of pulmonary fibrosis induced by the intratracheal instillation of bleomycin have been well established and widely used for studying the mechanisms underlying fibrosis and potential therapeutic agents (Jordana et al., 1988;Sakanashi et al., 1994;Moeller et al., 2008). Several studies using microarrays have been performed to evaluate gene expression patterns in the lungs after bleomycin instillation and identify the major genes involved in the progression of pulmonary fibrosis (Kaminski et al., 2000;Zuo et al., 2002;Katsuma et al., 2001;Pottier et al., 2007). These studies have provided information about genes that play central roles in the progression of fibrosis over time in a mouse model. Although genomic approaches using bleomycin-induced pulmonary fibrosis animal models have been useful for understanding the molecular mechanisms underlying fibrosis and for identifying fibrogenic markers, these approaches have limitations related to the vast data sets generated and the difficulty of replicating progressive fibrosis in animal models. Furthermore, recent studies aimed at eluc

[17] Exploring therapeutic targets for molecular therapy of idiopathic pulmonary fibrosis

• Authors: Yue Li, Congshan Jiang, Wenhua Zhu, Shemin Lu, Hongchuan Yu et al.
• Year: 2024
• Venue: Science Progress
• URL: https://www.semanticscholar.org/paper/db2853a4caa1beb6b56a994ba01253577a388786
• DOI: 10.1177/00368504241247402
• PMID: 38651330
• PMCID: 11036936
• Citations: 6
• Summary: The research platform, including cell and animal models involved in molecular therapy studies of idiopathic pulmonary fibrosis as well as the promising therapeutic targets and their development progress during clinical trials are reviewed.
• Evidence snippets:
• Snippet 1 (score: 0.501) > Idiopathic pulmonary fibrosis is a chronic and progressive interstitial lung disease with a poor prognosis. Idiopathic pulmonary fibrosis is characterized by repeated alveolar epithelial damage leading to abnormal repair. The intercellular microenvironment is disturbed, leading to continuous activation of fibroblasts and myofibroblasts, deposition of extracellular matrix, and ultimately fibrosis. Moreover, pulmonary fibrosis was also found as a COVID-19 complication. Currently, two drugs, pirfenidone and nintedanib, are approved for clinical therapy worldwide. However, they can merely slow the disease's progression rather than rescue it. These two drugs have other limitations, such as lack of efficacy, adverse effects, and poor pharmacokinetics. Consequently, a growing number of molecular therapies have been actively developed. Treatment options for IPF are becoming increasingly available. This article reviews the research platform, including cell and animal models involved in molecular therapy studies of idiopathic pulmonary fibrosis as well as the promising therapeutic targets and their development progress during clinical trials. The former includes patient case/control studies, cell models, and animal models. The latter includes transforming growth factor-beta, vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factor, lysophosphatidic acid, interleukin-13, Rho-associated coiled-coil forming protein kinase family, and Janus kinases/signal transducers and activators of transcription pathway. We mainly focused on the therapeutic targets that have not only entered clinical trials but were publicly published with their clinical outcomes. Moreover, this work provides an outlook on some promising targets for further validation of their possibilities to cure the disease. Graphical abstract Therapeutic targets for molecular therapy of idiopathic pulmonary fibrosis.

[18] Idiopathic Pulmonary Fibrosis: Pathogenesis and the Emerging Role of Long Non-Coding RNAs

• Authors: Marina R. Hadjicharalambous, M. Lindsay
• Year: 2020
• Venue: International Journal of Molecular Sciences
• URL: https://www.semanticscholar.org/paper/ed2b2741fecf7bc8fcb573d9a0eea180bca01326
• DOI: 10.3390/ijms21020524
• PMID: 31947693
• PMCID: 7013390
• Citations: 57
• Influential citations: 1
• Summary: An overview of the emerging role of long non-coding RNAs (lncRNAs) in the development of IPF is provided.
• Evidence snippets:
• Snippet 1 (score: 0.496) > Fibrosis is a pathophysiological condition that can affect nearly every organ in the human body where irregular and excessive accumulation of scar tissue leads to organ failure and potentially death as seen in the final stages of fibrotic diseases such as pulmonary [1], cardiac [2], nephrotic [3], and hepatic fibrosis [4]. In combination with genetic factors, tissue injuries may provoke the development of fibrosis including exposure to damaging environmental stimuli such as irritants, smoke, radiation, viral, and bacterial infections [5,6]. > Idiopathic pulmonary fibrosis (IPF) is a progressive chronic interstitial lung disease (ILD) which is characterized by scar tissue accumulation, and therefore thickening of the normal lung walls, leading to impaired gas exchange and restricted ventilation. IPF is a disease of unknown aetiology, which makes the development of effective drug treatments particularly challenging [5]. Nonetheless, scientists have been intensively researching the molecular and cellular mechanisms of the disease and, although the pathogenesis of IPF is still unclear, several theories regarding the pathophysiology of IPF have been proposed [7]. > As is the case with most ILDs, inflammation was initially thought to be the major player in IPF until unresponsiveness to anti-inflammatory medications prompted the re-evaluation of this idiom [8,9]. However, the presence of immune cells in IPF lungs has been a consistent pathological finding and could be important in the development of the disease [10][11][12][13][14]. The histology of fibrotic lungs also indicates irreversible accumulation of scarred tissue characterized by collagen deposition and other alterations to the extracellular matrix (ECM) which dramatically remodels the lung architecture by stiffening the distal airspaces and parenchyma [5]. It has been suggested that lung fibrosis could be provoked by a number of different cell types including epithelial cells, fibroblasts, myofibroblasts, and immune cells [1].

Notes

• This provider combines search_papers_by_relevance with snippet_search.
• No synthesis or second-stage model call is performed.